There is a growing interest in macrocyclic molecules that may be used as scaffolds in the combinatorial synthesis of receptor molecules. Many macrocyclic molecules have been synthesised. However, in many cases, their synthesis is difficult and/or relatively inflexible towards functionalisation. For some recent examples of unsymmetrically substituted macrocycles, see Rasmussen et al, J. Tet. Lett. (1999) 40: 3511; Höbger et al., Chem. Eur. J. (1999)5:1686; Shu et al, J. Org. Chem. (1999) 64: 2673; and Cho et al, Bioorg. Med. Chem. (1999)7: 1171. Cho et al discloses cyclic and linear oligocarbamates. Only in the case of cyclic peptides have stepwise synthesis, facile functionalisation of the building blocks, and solid phase synthesis been reported.
Some known macromolecules are based on triazine. Oligomers and cyclic molecules of this type are disclosed by Lipkowski et al, Chem. Commun. (1999) 1311; Ichihara et al, Chem. Letters (1995) 631; Mathias et al, J. Am. Chem. Soc. (B1994) 116: 4326; and Anelli et al, J. Org. Chem. (1984), 49: 4197. In particular, Mathias et al discloses linear triazine-based macromolecules, capable of supramolecular aggregation. Ichihara et al discloses triazine-linked porphyrins. Lipkowski et al discloses compounds that form a [2×2] hydrogen-bonded grid.
Known macrocycles include those of the formula where X is a ring which may bear a group R1, Y is a linker which optionally bears a group R2, and m is an integer. Thus, Rasmussen et al discloses compounds in which X is a benzene ring, R1 is H, Y is peptidic, R2 is a functional group, and m is 3, for combinatorial applications. Anelli et al discloses compounds in which X is triazine, R1 is Cl and m is 2, as intermediates to triply-bridged derivatives, capable of molecular recognition and of use as phase-transfer catalysts.